Tuesday 20th April 2021 | PRESS RELEASE; translation MIKE SMITH
The Carlos III Institute of Health (ISCIII), a public research body under the Ministry of Science and Innovation and the Ministry of Health, are promoting a clinical trial, called CombivacS, which will analyze the possible protective effect and safety of providing a dose of COVID-19 messenger RNA vaccine (BioNtech / Pfizer) to individuals who have already received a first dose of the AstraZeneca laboratory vaccine after a minimum of 8 weeks have elapsed since that dose.
The clinical trial, which has been launched following the discontinuation of AstraZeneca vaccination in people under 60 years of age, seeks to provide scientific evidence to support decision-making regarding a possible alternative to complete immunization in these people.
In other words, the study aims to clarify whether people who have received the first dose of AstraZeneca have generated enough antibodies or whether a booster dose with another vaccine is needed.
During the clinical development of the vaccines Comirnaty (Pfizer) and Vaxzevria (AstraZeneca) different studies have been developed to define the dose, efficacy, safety and conditions of use of each of them individually.
Following their authorization by the health authorities, both have been available for some time and are being administered in Europe, but so far, no clinical data are available on their possible combined use. Joint use seems possible and even desirable, as they are vaccines that act with different mechanisms of action and there is evidence that this approach to other diseases may be beneficial, but it is necessary to conduct clinical trials like this to verify this. The CombivacS study is one of the first clinical trials to analyze the safety and immunogenicity of such combined guidelines.
CombivacS will be promoted, coordinated and funded by ISCIII, managed by its Clinical Research Platform and will be developed in five hospitals: La Paz and Clínico San Carlos in Madrid; Vall d’Hebron and Clínic, in Barcelona, and Cruces in Vizcaya. The National Centre for Microbiology (CNM) of the ISCIII will act as the central laboratory of the trial, which has had the scientific advice of the Spanish Agency for Medicines and Health Products (AEMPS). The AEMPS, after the approval of the protocol by the Ethics Research Committee with Medicines (CEIm) of the La Paz University Hospital in Madrid, has issued the relevant authorizations for its implementation.
This is a comparative, randomized, and adaptive two phase clinical trial to assess the safety and immunogenicity (ability of the immune system to respond successfully to an infection) of a dose of the vaccine called Comirnaty (Pfizer) in people who have previously received a dose of the vaccine Vaxcevria (AstraZeneca). In this way, the study analyzes the possible combination of more than one vaccine (heterologous vaccination schedule), with different mechanisms of action, to complete the desired immunization. The starting hypothesis is that the mentioned immunogenicity will be higher in the group that receives two different doses of vaccines compared to the single dose.
The primary objective of the trial is therefore to test whether there is a significant 14-day increase in antibody counts against SARS-CoV-2 in people who have already received a dose of Vaxzevria (AstraZeneca) vaccine after receiving a dose of Comirnaty (Pfizer). To evaluate this possible increase in antibodies, the number of antibodies in a group of people who have been previously vaccinated with a single dose of Vaxzevria (AstraZeneca) but will not initially receive the dose of Comirnaty (Pfizer) will be analyzed simultaneously.
600 people selected at random
CombivacS will involve 600 randomly selected individuals who have received a dose of Vaxzevria (AstraZeneca) vaccine, provided that a minimum of 8 weeks have elapsed since that dose until the start of the trial and they are under 60 years of age. For logistical reasons, only people resident in the provinces where the five participating hospitals are located will be eligible. In any case, the first results are expected to be available five weeks after the start of the trial. If these results are favourable in safety and efficacy to the sequential vaccination schedule, a dose of Comirnaty will be offered to all participants in the control group.
Therefore, volunteers divided into two groups will participate in the trial, to which they will be randomly assigned. On the one hand, group 1 or intervention group, consisting of 400 people, will receive a dose of the vaccine Comirnaty (Pfizer), followed by 28 days of clinical observation and antibody analysis for one year.
For its part, group 2, which will consist of 200 people, will not initially receive any vaccine. This group 2 will act as a control group, all monitoring, safety and analysis procedures being identical to those of the experimental group. The comparison of the immune response between the two groups will be performed on analysis obtained 14 days after the inclusion of each volunteer, without prejudice to other very comprehensive analysis that will be performed over a year.
Consequently, and given that the 600 participants will need a minimum of 7 days to join the study and that thousands of samples must be analyzed, results are not expected to be obtained within four weeks of the first person receiving a dose of Comirnaty (Pfizer). In any case, if the results suggest it, 28 days after the start of the study, the Pfizer vaccine will be offered to all patients who did not initially receive it (group 2).
The National Centre for Microbiology-ISCIII will act as the central testing laboratory and responsible for the analysis and interpretation of antibody numbers. Thus, biological samples from the participants will be sent to this center to proceed with the determination of antibodies and neutralizing antibodies against SARS-CoV-2 as an indicator of protection against COVID-19.
Additionally, this study will answer other scientifically relevant questions. Therefore, among the secondary objectives, the researchers seek to obtain knowledge about the immune response conferred by the sequential combination of both vaccines over a year, as well as protection against SARS-CoV-2 variants at 14 and 28 days after completing the vaccination, among other issues.